Road traffic noise is an important source of noise annoyance in the community. We performed a meta-analysis to assess whether there is an association between noise annoyance from road traffic noise and cardiovascular diseases (arterial hypertension and ischemic heart disease) in adult population. The meta-analysis included studies that: a. had noise annoyance as exposure, quantified either as "annoyed versus non-annoyed" or with various scales collected by standardized questionnaires; b. arterial hypertension or ischemic heart disease as outcome; c. had included only adult population (age >18 years); d. the studies had to have as effect size odds ratios or relative risk. From the individual studies those odds ratios were selected for meta-analysis which compared most distant categories. Eight studies that fulfilled criteria published between 1992 and 2006 were included in the meta-analysis: 6 studies had a cross-sectional design, 1 study had a case-control-design and 1 study had a cohort design. Increased annoyance was significantly associated with arterial hypertension (pooled risk estimate = 1.16, 95% confidence interval 1.02-1.29) while the association with ischemic heart disease did not reach statistical significance (pooled risk estimate = 1.07, 95% confidence interval 0.99-1.14). No publication bias was evidenced. The results of this meta-analysis demonstrated the existence of a positive and significant association between noise annoyance from road traffic and the risk of arterial hypertension and a positive yet insignificant association between noise annoyance and the risk of ischemic heart disease.

Cardiovascular disease is a leading cause of mortality and morbidity worldwide. [1] The traditional cardiovascular risk factors account for only half of the observed variance in the incidence of myocardial infarction. [2],[3] Noise is a ubiquitous companion in the human life and a major public health problem of modern times. In the European Union, approximately 30% of the population are still exposed to a day-night average of traffic noise exceeding 55 dB(A). [4] The noise exposure seems to be worsening when compared with the 15% of the population exposed to levels above 65 dB(A) in the early eighties. [5] Furthermore, European surveys have reported that nearly one-third of the working population is exposed to noise during daily work. [6] There is biological [7],[8] and epidemiological evidence [9],[10] pointing out to the possibility that chronic noise exposure may increase the cardiovascular risk. Road traffic noise is considered to be one of the most important sources of noise annoyance in the community. [11] Several models have been proposed to explain the effects of noise on human health. [5] The hypothesis of an increased cardiovascular risk by chronic noise exposure is based almost entirely on the general stress model. [12],[13],[14] While noise exposure can be described with physical measures, noise annoyance is a subjective parameter considered to reflect the internal exposure to noise. Noise annoyance may be a connecting point between noise as a physical stimulus and physiological/pathophysiological actions that it produces in human organism.

There is only limited information on the relationship between noise annoyance from road traffic and the risk of cardiovascular disease. Available studies on the relationship between noise annoyance from road traffic and cardiovascular diseases have given contradictory results or have been inconclusive due to failure to reach the level of statistical significance. Although the epidemiological evidence pointing out to the existence of an association between annoyance caused by road traffic noise and the incidence of cardiovascular diseases has recently increased, [9],[15] the current level of evidence could be considered supportive rather than definitive. Thus, to further assess the association between noise annoyance and cardiovascular diseases, we used the meta-analytic methodology to summarize the results of individual studies. The primary objective of our meta-analysis was to assess whether there is an association between noise annoyance from road traffic noise and cardiovascular diseases - arterial hypertension and ischemic heart disease (myocardial infarction and angina pectoris) - in adults.

Methods

Search strategy

This meta-analysis was conducted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group guideline standards. [16] Medline (accessed by PubMed), Chochrane, Scopus and Google Scholar were searched in November 2009 for publications that reported the association between noise annoyance and arterial hypertension or ischemic heart disease. No restriction in time was imposed. To identify these publications, these data sources were searched with the following terms: noise annoyance, road traffic or transportation, cardiovascular disease, coronary artery disease, ischemic heart disease, acute coronary syndrome, myocardial infarction, angina pectoris and arterial hypertension. The reference lists of the retrieved studies were searched for further publications. Because of the low number of identified publications, in addition, the reference lists of two meta-analyses on the association between noise exposure and cardiovascular diseases were searched. [9],[10]

Criteria for study selection

For this meta-analysis, original studies that have reported the influence of noise annoyance from road traffic noise on arterial hypertension or ischemic heart disease were included. Studies on noise annoyance from other sources (occupational, industry, air, railway or neighborhood noise) were not included in this meta-analysis.

Inclusion criteria

To be included in the meta-analysis, studies had to report 1) as exposure: noise annoyance, quantified either as "annoyed versus non-annoyed" or with various scales such as 5-step "ICBEN scale" [17] collected by standardized questionnaires; and 2) as outcome: arterial hypertension or ischemic heart disease by the following criteria: a) diagnosis by a physician; b) being under active treatment with specific drug; c) having evidence through physical examination of the subjects and laboratory measurements (blood samples, electrocardiographic, echocardiographic or blood pressure measurement) and d) through self-report; 3) the investigation had to be performed in the adult population only (age > 18 years); 4) the studies had to have as effect size odds ratios or relative risk.

Exclusion criteria

Excluded from the meta-analysis were: 1) studies that have evaluated noise exposure only with physical characteristics (strength, intensity, distance from the source); 2) studies without quantification of noise annoyance or health outcome; 3) children studies (participants under 18 years of age as accepted by the American Academy of Pediatrics). Children were excluded for two reasons: first, cardiovascular diseases are extremely rare in children and second, the findings in children are difficult to interpret with regard to possible health effects in their later life. [10] 4) Studies in which the association between noise annoyance and cardiovascular disease was reported as a mean difference or correlation were not included.

Data extraction and validity assessment

For data collection, data extraction sheets were developed and the following information was obtained for each study.

The total score was assessed as: very good ≥10 points, good 6-9 points and fair ≤5 points. Studies were selected and data were extracted independently by two reviewers (DT and AN). Disagreements were resolved by consensus.

Statistical analysis

From the cardiovascular diseases, association between noise annoyance and the risk of arterial hypertension and ischemic heart disease (myocardial infarction or angina pectoris) was investigated. The selected effect size was odds ratio or relative risk with 95% CIs because these effect sizes were most commonly reported in studies. When odds ratios were reported for several annoyance scales, those comparing most distant scales (i.e., scales 5 to 1 in a 5-scale rating) were included in this meta-analysis. In studies that have performed separate analyses for day and nighttime, the odds ratios for nighttime were obtained and included in the analysis. When information on nighttime was missing, odds ratio(s) for daytime were included into the analysis. Due to differences in design, study populations and in used noise annoyance scale(s), both a fixed and a random effects model, according to the method of DerSimonian and Laird, was used. [18] Heterogeneity was explored using the chi-square test. The quantity of heterogeneity across studies was measured by the I2 statistic as proposed by Higgins. [19] Heterogeneity in studies was considered as low when I2 less than 25%, as moderate when I2 was between 25% and 50%, and high when I2 was greater than 50%. [19] Publication bias was assessed with respect to the primary outcome of interest using the Begg adjusted rank correlation test according to the method of Begg and Mazumdar [20] and regression asymmetry test by Egger et al. [21] The funnel plots were constructed to evaluate publication bias. A sensitivity analysis was performed by assessing the contribution of individual studies to the summary effect estimate with respect to the primary outcome. This was done by excluding each trial, one at a time, and computing meta-analysis estimates for the remaining studies. Results were considered statistically significant at P < 0.05. Statistical analyses were performed with Stata software, version 9.2 (Stata Corp., College Station, TX, USA).

Results

Eligible studies

Of the 271 potentially relevant studies after title and abstract evaluation, reference and related articles' search and an unpublished meta-analysis, an initial 19 studies were identified. Of them, 11 studies were excluded for various reasons [Figure 1]. Thus, eight studies were finally included in the meta-analysis. [22],[23],[24],[25],[26],[27],[28],[29] Characteristics of the included studies are shown in [Table 1]. Of them, six studies had a cross-sectional design, one study had a case-control design and one study was a cohort study. Three studies included only male participants, whereas the remaining five studies included both male and female subjects. The sample sizes of studies varied from 375 to 4320 subjects and the included subjects were from 18 to 90 years of age. The cardiovascular outcome was arterial hypertension in six studies, myocardial infarction in seven studies and angina pectoris in four studies. In six studies, more than one outcome was investigated. All the studies were adjusted for potential confounding variables, which varied from 3 variables (in the studies by Lercher et al. [23] and Bellojevic et al. [25] ) to 11 variables (in the study by Babisch et al.). [28]

Table 1: Main characteristics of the studies included in the meta-analysis on noise annoyance and cardiovascular diseases

As shown in [Table 2], six of eight included studies were published in peer-reviewed journals. Response rate was reported in six studies and varied from 62 to 86%. [Table 2] summarizes the data on quality assessment.

Table 2: Assessment of methodological quality of studies included in the meta-analysis on noise annoyance and cardiovascular diseases

[Table 3] shows the results of the individual studies. Noise annoyance was mostly assessed using a 5-point scale, but in analysis, categories were often combined. The reference category mostly consisted of participants who reported to be not at all or only little annoyed, while the most distant category in general included participants who reported being pretty much, very or strongly annoyed. However, in two studies, the most distant category included in addition moderately annoyed subjects, and in one study odds ratios were only given per unit on a 5-point scale.

The relationship between noise annoyance and arterial hypertension was investigated in six studies [Table 3]. In one study, the association between noise annoyance and arterial hypertension was investigated only in male participants, in three studies male and female participants were analyzed together, and two studies provided separate analyses for male and female participants. One study performed separate analyses according to age of participants, 18-59 years and over 60 years. There was a significant positive association between noise annoyance and the increased risk of arterial hypertension. The pooled risk estimate for association between noise annoyance and arterial hypertension was 1.16 with 95% CI 1.02, and 1.29 using the random effects model; P = 0.006 [Figure 2]. The analysis of sensitivity through exclusion of the studies one-by-one and calculating the pooled estimate for those remaining yielded similar overall estimates (from 1.11 to 1.56).

The relationship between noise annoyance and ischemic heart disease was investigated in all included studies. In seven studies, the outcome was defined as myocardial infarction and in one study, a broader definition including moderate Q waves was applied. In one study, noise annoyance was deleted from the statistical model due to an automatic variable selection process, and thus, no risk estimate was given. Two studies provided separate analyses for male and female participants and one study provided separate analyses according to age groups between 18 and 59 years and over 60 years. The pooled risk estimate of the association between noise annoyance and ischemic heart disease was 1.07 with 95% CI 0.99-1.14 and P = 0.055, showing the existence of a strong trend for an association between noise annoyance and ischemic heart disease. The forest plot is shown in [Figure 3].

In one study, [28] the association between noise annoyance and myocardial infarction was reported for nighttime and daytime separately. In sensitivity analysis, we repeated the calculation of the overall estimate by using the daytime results of this study [OR of 1.04 (0.97-1.12) for men and 1.03 (0.90-1.18) for women] and reached a pooled estimate of 1.04 (0.98-1.10), heterogeneity I2 = 0.0%, P = 0.94. The sensitivity analysis yielded similar overall risk estimates after exclusion of individual studies one-by-one (overall risk estimates between 1.01 and 1.10).

Publication bias

There was no evidence of publication bias in the included studies either for association between noise annoyance and arterial hypertension (P = 0.97 by Egger's test) or ischemic heart disease (P = 0.99 by Egger's test). The funnel plots are shown in [Figure 4].

The findings of this meta-analysis provide an indication of the existence of an association between noise annoyance and cardiovascular diseases. With regard to arterial hypertension, the current meta-analysis showed the existence of a significant positive association between the noise annoyance scale and this cardiovascular disorder. On the other hand, we observed a positive, yet statistically insignificant, association between the noise annoyance and the risk of ischemic heart disease. The low degree of heterogeneity between the included studies and the lack of publication bias are reassuring that the findings of current meta-analysis are not influenced by these two factors.

Evidence from other studies

Other studies which are not included in this meta-analysis due to methodological reasons suggest the existence of a positive association between noise annoyance and risk of cardiovascular diseases. [31],[32],[33],[34],[35],[36] Neus et al. [32] demonstrated that noise sensitive subjects annoyed by road traffic showed higher increases of blood pressure and that there was a significant association between subjective reaction to noise and frequency of antihypertensive treatment in the control area. Herbold et al. [33] using subjective rating of type of road reported a higher prevalence of arterial hypertension in roads with high exposure to noise compared to roads with low exposure to noise [adjusted odds ratio 1.32 (1.02-1.71)]. Ising et al. [34] studying occupational noise reported a progressive increase in the relative risk for myocardial infarction from a relative risk of 1.0 (reference) for low noise category (refrigerator/typewriter) to 3.8 (2.68-5.44) for high noise (pneumatic drill) category. A recent study by Björk et al. [35] showed that in annoyed subjects from road traffic noise, there is a significant association between average noise level and treatment for arterial hypertension in the last 12 months (7.9% in low noise level vs. 14.7% in high noise level; P = 0.02). Erikson et al. [36] investigating the impact of noise from air traffic found increased risk of arterial hypertension in not annoyed subjects. To explain this controversial finding, they suggested that concomitant exposure of these subjects to noise from other sources may have interfered. [36]

Thus, the results of these studies and the current meta-analysis demonstrate the existence of a positive association between annoyance caused by road traffic and risk of cardiovascular diseases. In a broader prospect, the results of current meta-analysis as well as the recent meta-analysis by van Kempen [9] and the recent review by Babisch [10] increase the evidence on the impact of noise, estimated either by objective (sound level assessment) or internal exposure (annoyance) on the increased risk of cardiovascular diseases in community.

Biological mechanisms

There is evidence that internal reaction to noise exposure or noise annoyance is related to the activation of autonomous nervous system and neuroendocrine system, resulting in the elevation of circulating catecholamine and cortisol levels. Irrespective of their triggering source, arousal of sympathetic nervous system increases the circulating levels of catecholamines which increase blood pressure (as an acute effect), and through their properties to increase cardiac output and cause vascular hypertrophy, [37] predispose for fixed increase in blood pressure and arterial hypertension if prolonged in time. Apart from causing arterial hypertension, disproportional and prolonged activation of sympathetic nervous system causes cardiac hypertrophy, reduction in plasma volume, increased vascular hypertrophy, changes in hematocrit and blood platelets predisposing for thrombosis, insulin resistance and dyslipidemia predisposing for coronary artery disease, and coronary spasm and endothelial dysfunction predisposing for acute coronary syndromes such as acute myocardial infarction. [37],[38],[39] An increase in adrenergic drive may have deteterious effects on renal circulation, favoring blood pressure elevation through an increase in sodium resorption. [40]

Elevated levels of cortisol may cause arterial hypertension through activation of rennin-angiotensin-aldosterone axis, [41] enhancement of cardiovascular inotropic and pressor activity of catecholamines and other vasoactive substances, [42] and suppression of vasodilator substances such as nitric oxide, kallikrein and prostacyclin, [43],[44] which leads to increases in peripheral vascular resistance. Moreover, chronically elevated cortisol level leads to insulin resistance and hyperinsulinemia which is involved in the promotion of atherogenesis and endothelial dysfunction. [45]

Apart from the elevation of circulating levels of stress hormones, noise exposure causes other metabolic alterations, in particular, alterations in blood lipids which are more pronounced in noise annoyed subjects. [46] Hypothetically, it may be said that noise annoyance by being an internal reaction to noise exposure, as is the case with stress hormones and mediators and lipid alterations, may be considered as an estimate of overall internal exposure to noise.

Limitations

We recognize that the current meta-analysis has several limitations. While we employed an intensive literature search, we were only able to find few studies on this issue. Because of the low number of publications, subgroup analyses, specifically separate analyses for males and females or for specific study types, were not possible. The results with respect to ischemic heart disease are influenced heavily (by 64%) by the results for males in one large study. [26] After exclusion of this study, the association between noise annoyance and ischemic heart disease was further attenuated (OR = 1.01, 95% CI 0.88-1.13). Furthermore, the pooled risk estimate was slightly reduced when the results for daytime annoyance were used instead of nighttime annoyance from this study. [28] However, it might be argued that particularly for employed subjects, nighttime noise annoyance may be more important, since during night, more time is spend at home than during the daytime. Most of the included studies had a cross-sectional design. It is known that cross-sectional studies are suboptimal for searching the cause of diseases since the simultaneous collection of data cannot establish the chronology of exposure and disease. Although all studies included in this meta-analysis performed adjustment for a various number of potential confounders and all risk estimates were adjusted, the list of cardiovascular risk factors included in these studies was incomplete. No adjustment for actual noise levels was provided, which would be counterproductive since the adjustment for noise level as an important predictor of annoyance could produce spuriously negative results. The evaluation of the association between noise annoyance and disease status independent of noise level was not the aim of the meta-analysis. Of note, Babisch et al. [26] have demonstrated that pre-existing cardiovascular disease is an important modifier of the relation between noise annoyance and health outcomes. In subjects with pre-existing cardiovascular disease, adjusted odds ratio in subjects often plus always annoyed versus those never annoyed was 2.45 (95% CI 1.13-5.31) compared with 0.95 (0.52-1.75) in subjects without pre-existing ischemic heart disease. [26] Along the same lines, it has been reported that occupational noise affects the resting blood pressure, especially in subjects with a familial history for arterial hypertension. [47] The exaggerated effects of noise annoyance on cardiovascular disease in subjects with pre-existing disease, as reported in these studies, may be explained by inherent susceptibility of these subjects due to either reduced reserve to cope with noise stress or to further increases in psychophysiological arousal which may be already higher in subjects with pre-existing cardiovascular disease. Alternatively, subjects with pre-existing disease may give exaggerated answers about their annoyance status, a modality that raises the possibility of recall bias which is an important limitation of studies based on subjective ratings. [26] Especially in case of association between noise annoyance and arterial hypertension, the possibility of an inverse association between noise annoyance and arterial hypertension, i.e., hypertension-induced annoyance cannot be excluded. Although noise annoyance was assessed by a 5-point scale in most studies, the extreme ends of the scale (highest vs. lowest) are most frequently compared. Thus, the assessment of cardiovascular outcome across the entire scale allowing a risk calculation per unit of noise annoyance scale could not be performed. Hence, a dose-effect relationship, which is an important tool in investigating the causality of the relationship between noise annoyance and cardiovascular disease, cannot be assessed in this meta-analysis. The interpretation of the pooled estimate is hindered by the different comparison categories used in the individual studies. Looking at [Table 3], an interpretation of the pooled estimator in terms of the relative risk of subjects reporting "strong or extreme annoyance" versus subjects reporting "no or little annoyance" seems to be the most plausible and a conservative approach to quantification. In some studies, the outcome was subjectively (self-reported) assessed which might have resulted in overreporting, especially for arterial hypertension. As the overreporting most probably is non-differential, i.e., is not associated with exposure status, this misclassification will result in a bias toward a null effect.

Conclusions

The results of this meta-analysis suggest the existence of a positive and significant association between noise annoyance from road traffic and arterial hypertension. Specifically, this meta-analysis showed that subjects exposed to higher categories of noise annoyance had a significant 15.5% increase in risk of arterial hypertension and a nearly significant 7% increase in the risk of ischemic heart disease. Although the current meta-analysis provides an indication for the existence of an association between noise annoyance and increased risk for cardiovascular diseases, additional studies are needed to further confirm the casual relationship between noise annoyance and cardiovascular disease. Furthermore, impact of age and sex and other potential modifiers as well as investigation of a dose-response relationship remain an object of future studies.